Miola, Alessandro

ABSTRACT Introduction Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), initially developed for type 2 diabetes, have shown promise in improving renal outcomes in patients with and without diabetes. However, their effect on lithium‐associated kidney dysfunction remains unknown. Methods This historical cohort study included patients from Mayo Clinic (2001–2023) with mood disorders who received lithium for ≥ 6 months and later used SGLT2i for ≥ 1 month. Data on SGLT2i use and lithium treatment were extracted from electronic health records. Serum creatinine values were used to calculate estimated glomerular filtration rate (eGFR) trajectories. Linear mixed‐effects models with piecewise linear splines were used to estimate eGFR slopes before and after SGLT2i initiation, adjusted for age and sex. Results Fifty‐six patients (mean age 57.4 years, 46.4% female), predominantly with bipolar disorder (87.5%), were included. The mean eGFR, measured nearest to SGLT2i initiation, was 77.9 ± 26.0 mL/min/1.73 m 2 , and the mean duration of SGLT2i use was 19.5 ± 17.8 months. Before SGLT2i initiation, eGFR declined at a rate of −1.43 mL/min/1.73 m 2 per year ( p < 0.001). After initiation, eGFR increased by 0.69 mL/min/1.73 m 2 per year, reflecting a + 2.13 change ( p = 0.025). Sensitivity analyses, including only patients on lithium at SGLT2i initiation ( n = 22) or who had > 1 year of SGLT2i use ( n = 29) showed similar, though non‐significant, changes in slopes. Conclusion SGLT2i treatment was associated with a significant improvement in eGFR trajectory in patients with mood disorders who received long‐term lithium therapy. These findings suggest a potential role for SGLT2is in mitigating lithium‐associated kidney dysfunction and highlight the need for randomized controlled trials in this population.

Abstract Background Bipolar disorder (BD) is associated with impairments in facial emotion recognition (FER), affecting social functioning and quality of life. Understanding FER deficits in BD is crucial for tailoring interventions and improving treatment outcomes. This systematic review and meta-analysis aims to evaluate FER differences among individuals with BD, unaffected first-degree relatives (FDRs), and healthy controls (HCs), exploring predictors related to patient and study characteristics. Methods We systematically searched PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO databases from inception to March 28, 2024. Random-effects meta-analyses were conducted to explore differences in accuracy and reaction time during FER identification and discrimination tasks. Results A total of 100 studies were included, comprising 4920 individuals with BD (females = 56%, mean age = 34.1 ± 9.1), 676 FDRs (females = 55%, mean age = 36.1 ± 12), and 4909 HCs (females = 53.2%, mean age = 32.5 ± 9.5). Compared to HCs, adults with BD exhibited significantly lower accuracy (SMD = −0.47; 95% CIs = −0.56, −0.38) and higher reaction time (SMD = 0.57; 95%CIs = 0.33, 0.81) during facial emotion identification tasks. During facial emotion discrimination tasks, adults with BD had significantly lower accuracy than HCs (SMD = −0.59; 95%CIs = −0.78, −0.4), but similar speed. No significant differences were observed between BD and FDRs. Meta-regressions identified several predictors of FER performance, including manic symptom severity, stimulus duration, and presence of practice before task. Conclusions FER deficits appear to be a core feature of BD and require specialized, systematic assessment. Identifying these deficits may help guide interventions aimed at improving affective cognition and social outcomes in individuals with BD.

ABSTRACT Objectives To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement. Methods 2280 individuals living with BD type I or II (62% women; 67.5% BD‐I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative‐valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term. Results After adjusting for age, sex, and recruitment site, SDoH‐related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH‐related stress (i.e., lack of family support, financial problems, health coverage and access problems). Conclusions The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.